This invention relates to novel triazole derivatives which have antifungal activity and are useful in the treatment of fungal infections in humans.
In particular the invention relates to certain 3-heterocyclylmethylthio- and 3-arylmethylthio-1-triazolyl-2-propanol derivatives which are particularly effective as oral and topical agents for the treatment of fungal diseases in humans and other animals, and to pharmaceutical compositions containing such compounds.
Concurrently filed U.S. patent applications of Richardson and Gymer entitled "Antifungal S-Ethers of 2-Aryl-3-Mercapto-1-(1H-1,2,4-Triazol-1-yl)Propan-2-Ols and Corresponding Sulfoxides and Sulfones", and of Richardson and Whittle entitled "Triazole Antifungal Agents", and identified by Ser. Nos. 479,524, filed 3/28/83 and 479,525, filed 3/28/85, respectively, are directed to related S-ethers of 2-aryl-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-propan-2-ols.
European patent application No. 0061835 discloses a broad class of triazole and imidazole compounds having the general formula: ##STR2## wherein R.sup.1 and R.sup.2, which may be the same or different, are hydrogen, alkyl, optionally substituted cycloalkyl, cycloalkylmethyl, alkenyl, heterocyclyl, aryl or aralkyl optionally substituted with halogen, nitro, alkyl, haloalkyl, alkoxy, phenyl, phenoxy, benzyl, benzyloxy, halophenyl or haloalkoxy; R.sup.3 is hydrogen, alkyl, alkenyl, alkynyl, aralkyl or acyl; R.sup.4 and R.sup.5, which may be the same or different are hydrogen, alkyl, alkenyl or optionally substituted aryl; R.sup.6 and R.sup.7, which may be the same or different are hydrogen, alkyl, alkenyl or optionally substituted aryl; X is oxygen or sulfur or is SO or SO.sub.2 and Az is a 1,2,4- or 1,3,4-triazole or imidazole ring; and isomers, acid addition salts and metal complexes thereof.
The compounds are stated to possess fungicidal activity, principally as plant fungicides, and also to be plant growth regulators. There is also a brief reference that the compounds are useful for the treatment of candidiasis and human dematophyte infections.
We have discovered that a particular class of non-exemplified compounds within formula (A) wherein R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are H, X is S or SO and R.sup.2 is arylmethyl are surprisingly particularly effective as human antifungal agents and this property is not shared by the compounds wherein R.sup.2 is aryl, which are the only compounds where X is S exemplified in the European patent.
The invention also includes the corresponding heterocyclylmethyl derivatives which are not within the scope of the European patent application No. 0061835.